The actin cytoskeleton undergoes extensive remodeling during cell morphogenesis and motility. The small guanosine triphosphatase Rho regulates such remodeling, but the underlying mechanisms of this regulation remain unclear. Cofilin exhibits actin-depolymerizing activity that is inhibited as a result of its phosphorylation by LIM-kinase. Cofilin was phosphorylated in N1E-115 neuroblastoma cells during lysophosphatidic acid-induced, Rho-mediated neurite retraction. This phosphorylation was sensitive to Y-27632, a specific inhibitor of the Rho-associated kinase ROCK. ROCK, which is a downstream effector of Rho, did not phosphorylate cofilin directly but phosphorylated LIM-kinase, which in turn was activated to phosphorylate cofilin. Overexpression of LIM-kinase in HeLa cells induced the formation of actin stress fibers in a Y-27632-sensitive manner. These results indicate that phosphorylation of LIM-kinase by ROCK and consequently increased phosphorylation of cofilin by LIM-kinase contribute to Rho-induced reorganization of the actin cytoskeleton.

The small GTPase Rho induces the formation of actin stress fibres and mediates the formation of diverse actin structures. However, it remains unclear how Rho regulates its effectors to elicit such functions. Here we show that GTP-bound Rho activates its effector mDia1 by disrupting mDia1's intramolecular interactions. Active mDia1 induces the formation of thin actin stress fibres, which are disorganized in the absence of activity of the Rho-associated kinase ROCK. Moreover, active mDia1 transforms ROCK-induced condensed actin fibres into structures reminiscent of Rho-induced stress fibres. Thus mDia1 and ROCK work concurrently during Rho-induced stress-fibre formation. Intriguingly, mDia1 and ROCK, depending on the balance of the two activities, induce actin fibres of various thicknesses and densities. Thus Rho may induce the formation of different actin structures affected by the balance between mDia1 and ROCK signalling.

The small GTP‐binding protein Rho functions as a molecular switch in the formation of focal adhesions and stress fibers, cytokinesis and transcriptional activation. The biochemical mechanism underlying these actions remains unknown. Using a ligand overlay assay, we purified a 160 kDa platelet protein that bound specifically to GTP‐bound Rho. This protein, p160, underwent autophosphorylation at its serine and threonine residues and showed the kinase activity to exogenous substrates. Both activities were enhanced by the addition of GTP‐bound Rho. A cDNA encoding p160 coded for a 1354 amino acid protein. This protein has a Ser/Thr kinase domain in its N‐terminus, followed by a coiled‐coil structure approximately 600 amino acids long, and a cysteine‐rich zinc finger‐like motif and a pleckstrin homology region in the C‐terminus. The N‐terminus region including a kinase domain and a part of coiled‐coil structure showed strong homology to myotonic dystrophy kinase over 500 residues. When co‐expressed with RhoA in COS cells, p160 was co‐precipitated with the expressed Rho and its kinase activity was activated, indicating that p160 can associate physically and functionally with Rho both in vitro and in vivo.

There is currently much interest in the development of 'spintronic' devices, in which harnessing the spins of electrons (rather than just their charges) is anticipated to provide new functionalities that go beyond those possible with conventional electronic devices. One widely studied example of an effect that has its roots in the electron's spin degree of freedom is the torque exerted by a spin-polarized electric current on the spin moment of a nanometre-scale magnet. This torque causes the magnetic moment to rotate at potentially useful frequencies. Here we report a very different phenomenon that is also based on the interplay between spin dynamics and spin-dependent transport, and which arises from unusual diode behaviour. We show that the application of a small radio-frequency alternating current to a nanometre-scale magnetic tunnel junction can generate a measurable direct-current (d.c.) voltage across the device when the frequency is resonant with the spin oscillations that arise from the spin-torque effect: at resonance (which can be tuned by an external magnetic field), the structure exhibits different resistance states depending on the direction of the current. This behaviour is markedly different from that of a conventional semiconductor diode, and could form the basis of a nanometre-scale radio-frequency detector in telecommunication circuits.

Rho small GTPase regulates cell morphology, adhesion and cytokinesis through the actin cytoskeleton. We have identified a protein, p140mDia, as a downstream effector of Rho. It is a mammalian homolog of Drosophila diaphanous, a protein required for cytokinesis, and belongs to a family of formin‐related proteins containing repetitive polyproline stretches. p140mDia binds selectively to the GTP‐bound form of Rho and also binds to profilin. p140mDia, profilin and RhoA are co‐localized in the spreading lamellae of cultured fibroblasts. They are also co‐localized in membrane ruffles of phorbol ester‐stimulated sMDCK2 cells, which extend these structures in a Rho‐dependent manner. The three proteins are recruited around phagocytic cups induced by fibronectin‐coated beads. Their recruitment is not induced after Rho is inactivated by microinjection of botulinum C3 exoenzyme. Overexpression of p140mDia in COS‐7 cells induced homogeneous actin filament formation. These results suggest that Rho regulates actin polymerization by targeting profilin via p140mDia beneath the specific plasma membranes.